KR20020067701A - 3-아미노퀴나졸린-2,4-디온 항균제 - Google Patents

3-아미노퀴나졸린-2,4-디온 항균제 Download PDF

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Publication number: KR20020067701A
Authority: KR; South Korea
Prior art keywords: dione; amino; cyclopropyl; fluoro; quinazoline
Prior art date: 2000-01-24
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

KR1020027009515A

Other languages

English (en)

Korean (ko)

Inventor

폴 버드

에드먼드 리 엘스워쓰

다이 쿼크 은구옌

죠세프 피터 산체즈

하워드 다니엘 홀리스 쇼우알터

라제시와 싱히

마이클 앤드류 스티어

투안 퐁 트랜스

브라이언 모르간 왓슨

쥬디 이프

Original Assignee

워너-램버트 캄파니

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-01-24

Filing date

2000-12-12

Publication date

2002-08-23

2000-12-12 Application filed by 워너-램버트 캄파니 filed Critical 워너-램버트 캄파니

2002-08-23 Publication of KR20020067701A publication Critical patent/KR20020067701A/ko

Status Withdrawn legal-status Critical Current

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NMGODFWGUBLTTA-UHFFFAOYSA-N 3-amino-1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)N(N)C(=O)NC2=C1 NMGODFWGUBLTTA-UHFFFAOYSA-N 0.000 title abstract description 14
239000003242 anti bacterial agent Substances 0.000 title description 3
125000000217 alkyl group Chemical group 0.000 claims abstract description 77
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 52
125000003118 aryl group Chemical group 0.000 claims abstract description 49
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 32
229910052799 carbon Inorganic materials 0.000 claims abstract description 21
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 21
239000001257 hydrogen Substances 0.000 claims abstract description 20
229910004013 NO 2 Inorganic materials 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 15
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract 7
-1 (S) -3-aminopyrrolidin-1-yl Chemical group 0.000 claims description 543
150000001875 compounds Chemical class 0.000 claims description 303
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 114
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 97
238000000034 method Methods 0.000 claims description 65
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 50
239000004202 carbamide Substances 0.000 claims description 49
125000000547 substituted alkyl group Chemical group 0.000 claims description 42
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 40
SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 claims description 36
125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims description 31
125000006711 (C2-C12) alkynyl group Chemical group 0.000 claims description 31
125000005017 substituted alkenyl group Chemical group 0.000 claims description 31
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 28
125000004426 substituted alkynyl group Chemical group 0.000 claims description 27
125000001424 substituent group Chemical group 0.000 claims description 26
125000005843 halogen group Chemical group 0.000 claims description 25
241000124008 Mammalia Species 0.000 claims description 22
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 20
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 18
ZGCGNTZEVIIFAM-UHFFFAOYSA-N 1-fluoro-8-methylquinazoline-2,4-dione Chemical compound FN1C(=O)NC(=O)C2=C1C(C)=CC=C2 ZGCGNTZEVIIFAM-UHFFFAOYSA-N 0.000 claims description 17
YICYZJSYKMZSRN-UHFFFAOYSA-N 1-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FN1C(NC(C2=CC=CC(=C12)OC)=O)=O YICYZJSYKMZSRN-UHFFFAOYSA-N 0.000 claims description 16
RYECOJGRJDOGPP-UHFFFAOYSA-N Ethylurea Chemical compound CCNC(N)=O RYECOJGRJDOGPP-UHFFFAOYSA-N 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 12
208000035143 Bacterial infection Diseases 0.000 claims description 11
208000022362 bacterial infectious disease Diseases 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
239000003085 diluting agent Substances 0.000 claims description 10
239000000546 pharmaceutical excipient Substances 0.000 claims description 10
239000008194 pharmaceutical composition Substances 0.000 claims description 9
125000003107 substituted aryl group Chemical group 0.000 claims description 9
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 9
HTKQAYBIDKERJN-UHFFFAOYSA-N 1-methoxyquinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(OC)C2=C1 HTKQAYBIDKERJN-UHFFFAOYSA-N 0.000 claims description 8
RWFOOMQYIRITHL-UHFFFAOYSA-N 1-methylquinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)N(C)C2=C1 RWFOOMQYIRITHL-UHFFFAOYSA-N 0.000 claims description 8
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 7
125000004122 cyclic group Chemical group 0.000 claims description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 claims description 6
DCPYEEYKLICNTD-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=CC(F)=CC(C(NC2=O)=O)=C1N2C1CC1 DCPYEEYKLICNTD-UHFFFAOYSA-N 0.000 claims description 6
SMONLCFJGCJROJ-MNOVXSKESA-N 3-amino-7-[(3s)-3-[(1r)-1-aminoethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1[C@@H]([C@H](N)C)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C SMONLCFJGCJROJ-MNOVXSKESA-N 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 5
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
ILSRMENRGMPIHQ-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=CC(F)=CC(C(NC2=O)=O)=C1N2C1CC1 ILSRMENRGMPIHQ-UHFFFAOYSA-N 0.000 claims description 4
125000003386 piperidinyl group Chemical group 0.000 claims description 4
LBGAWTGOQQBAHW-UHFFFAOYSA-N 1-cyclopropyl-8-methylpyrido[4,3-d]pyrimidine-2,4-dione Chemical compound C1(CC1)N1C(NC(C2=C1C(=CN=C2)C)=O)=O LBGAWTGOQQBAHW-UHFFFAOYSA-N 0.000 claims description 3
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 3
UUDALWDRIFYZPM-UHFFFAOYSA-N 1h-pyridine-2,4-dione Chemical compound O=C1CC(=O)C=CN1 UUDALWDRIFYZPM-UHFFFAOYSA-N 0.000 claims description 3
125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
JASKKDJDJMQUCW-UHFFFAOYSA-N 3-amino-7-[4-(aminomethyl)piperidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CN)CC1 JASKKDJDJMQUCW-UHFFFAOYSA-N 0.000 claims description 3
BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 claims description 3
RYWUCROSFBWYGB-UHFFFAOYSA-N 1-cyclopropyl-6-fluoro-5,8-dimethylquinazoline-2,4-dione Chemical compound C1(CC1)N1C(NC(C2=C(C(=CC(=C12)C)F)C)=O)=O RYWUCROSFBWYGB-UHFFFAOYSA-N 0.000 claims description 2
PFSZPRDGUQBIJS-LURJTMIESA-N 3,5-diamino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6,8-difluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C1=C(F)C(N)=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1F PFSZPRDGUQBIJS-LURJTMIESA-N 0.000 claims description 2
HKNHNFKDEOQGLZ-UHFFFAOYSA-N 3,8-diamino-7-[3-(1-aminoethyl)pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-5-methylquinazoline-2,4-dione Chemical compound C1C(C(N)C)CCN1C1=C(F)C(C)=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1N HKNHNFKDEOQGLZ-UHFFFAOYSA-N 0.000 claims description 2
KGBQXGXVBHFICV-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-8-methoxy-7-[3-[(propan-2-ylamino)methyl]pyrrolidin-1-yl]quinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(CNC(C)C)C1 KGBQXGXVBHFICV-UHFFFAOYSA-N 0.000 claims description 2
ZRLLSDAIVJNZMQ-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-8-methoxy-7-pyrrolidin-1-ylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC1 ZRLLSDAIVJNZMQ-UHFFFAOYSA-N 0.000 claims description 2
FLYGUSNYKRVMER-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6-fluoro-8-methyl-7-pyrrolidin-1-ylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCCC1 FLYGUSNYKRVMER-UHFFFAOYSA-N 0.000 claims description 2
VLVSORUTOYXYIG-UHFFFAOYSA-N 3-amino-7-(2-amino-5-azaspiro[2.4]heptan-5-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N(C1)CCC21CC2N VLVSORUTOYXYIG-UHFFFAOYSA-N 0.000 claims description 2
QBAYAKOQUGQOHL-UHFFFAOYSA-N 3-amino-7-(3-amino-3-methylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(C)(N)C1 QBAYAKOQUGQOHL-UHFFFAOYSA-N 0.000 claims description 2
ONJJNQNMGCKRBJ-UHFFFAOYSA-N 3-amino-7-(3-amino-3-phenylpyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N(C1)CCC1(N)C1=CC=CC=C1 ONJJNQNMGCKRBJ-UHFFFAOYSA-N 0.000 claims description 2
NICJESYMFMNVRX-UHFFFAOYSA-N 3-amino-7-(3-amino-3-phenylpyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C12=C(Cl)C(N3CC(N)(CC3)C=3C=CC=CC=3)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 NICJESYMFMNVRX-UHFFFAOYSA-N 0.000 claims description 2
MYNASXNPNLIHST-UHFFFAOYSA-N 3-amino-7-(3-amino-4-fluoropyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(N)C(F)C1 MYNASXNPNLIHST-UHFFFAOYSA-N 0.000 claims description 2
LMKZWBWISAEVOS-UHFFFAOYSA-N 3-amino-7-(3-amino-4-methoxypyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound C1C(N)C(OC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1OC LMKZWBWISAEVOS-UHFFFAOYSA-N 0.000 claims description 2
SQVTZXOBPCVCIL-UHFFFAOYSA-N 3-amino-7-(3-amino-4-methoxypyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound C1C(N)C(OC)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1C SQVTZXOBPCVCIL-UHFFFAOYSA-N 0.000 claims description 2
RHLHZJMDAZKSES-UHFFFAOYSA-N 3-amino-7-(3-aminoazetidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CC(N)C1 RHLHZJMDAZKSES-UHFFFAOYSA-N 0.000 claims description 2
VPDDXYVQSVBBMT-UHFFFAOYSA-N 3-amino-7-(3-aminopiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCCC(N)C1 VPDDXYVQSVBBMT-UHFFFAOYSA-N 0.000 claims description 2
YKTNCTISKOJENP-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-5-methylquinazoline-2,4-dione Chemical compound O=C1N(N)C(=O)C=2C(C)=C(F)C(N3CC(N)CC3)=CC=2N1C1CC1 YKTNCTISKOJENP-UHFFFAOYSA-N 0.000 claims description 2
JFMXVEXEGIJVCH-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(N)C1 JFMXVEXEGIJVCH-UHFFFAOYSA-N 0.000 claims description 2
APNFNASNMSAHKF-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(C)=C1N1CCC(N)C1 APNFNASNMSAHKF-UHFFFAOYSA-N 0.000 claims description 2
MBXPBQAHLCCZOV-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-ethoxy-6-fluoroquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OCC)=C1N1CCC(N)C1 MBXPBQAHLCCZOV-UHFFFAOYSA-N 0.000 claims description 2
NLGWNSVFUWNXQX-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-fluoro-6-methoxyquinazoline-2,4-dione Chemical compound COC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(F)=C1N1CCC(N)C1 NLGWNSVFUWNXQX-UHFFFAOYSA-N 0.000 claims description 2
AEVLVLQRERPDHR-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-1-cyclopropyl-8-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=CC=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1F AEVLVLQRERPDHR-UHFFFAOYSA-N 0.000 claims description 2
GXQRPAGCOKWOTA-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-6-chloro-1-cyclopropyl-8-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=C(Cl)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1F GXQRPAGCOKWOTA-UHFFFAOYSA-N 0.000 claims description 2
LXAOHWSBPOQFAW-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-1-(cyclobutylamino)-6-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(NC3CCC3)C2=C1Cl LXAOHWSBPOQFAW-UHFFFAOYSA-N 0.000 claims description 2
IZSIJRQLAKGNBV-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1C(N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl IZSIJRQLAKGNBV-UHFFFAOYSA-N 0.000 claims description 2
GKVGMICZIRZYHZ-UHFFFAOYSA-N 3-amino-7-(3-aminopyrrolidin-1-yl)-8-chloro-6-fluoro-1-propan-2-ylquinazoline-2,4-dione Chemical compound FC=1C=C2C(=O)N(N)C(=O)N(C(C)C)C2=C(Cl)C=1N1CCC(N)C1 GKVGMICZIRZYHZ-UHFFFAOYSA-N 0.000 claims description 2
UCJVXLRCPAIDEL-UHFFFAOYSA-N 3-amino-7-(4-amino-2,3-dihydropyrrol-1-yl)-1-butan-2-yl-8-chloro-6-fluoroquinazoline-2,4-dione Chemical compound FC=1C=C2C(=O)N(N)C(=O)N(C(C)CC)C2=C(Cl)C=1N1CCC(N)=C1 UCJVXLRCPAIDEL-UHFFFAOYSA-N 0.000 claims description 2
UFFBMSWIXMBGJA-UHFFFAOYSA-N 3-amino-7-(4-aminopiperidin-1-yl)-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1CCC(N)CC1 UFFBMSWIXMBGJA-UHFFFAOYSA-N 0.000 claims description 2
ZDZWWQMQJYXBNK-PRHODGIISA-N 3-amino-7-[(3r,4s)-3-(aminomethyl)-4-fluoropyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-8-methoxyquinazoline-2,4-dione Chemical compound FC1=CC(C(N(N)C(=O)N2C3CC3)=O)=C2C(OC)=C1N1C[C@@H](F)[C@H](CN)C1 ZDZWWQMQJYXBNK-PRHODGIISA-N 0.000 claims description 2
YHGMEWWKLNOXML-MNOVXSKESA-N 3-amino-7-[(3s)-3-[(1r)-1-aminoethyl]pyrrolidin-1-yl]-1-cyclopropyl-6-fluoro-5-methylquinazoline-2,4-dione Chemical compound C1[C@@H]([C@H](N)C)CCN1C(C(=C1C)F)=CC2=C1C(=O)N(N)C(=O)N2C1CC1 YHGMEWWKLNOXML-MNOVXSKESA-N 0.000 claims description 2
DPVCHDCEWZUPRH-ZETCQYMHSA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-(cyclopropylamino)-5,8-difluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C1=CC(F)=C2C(=O)N(N)C(=O)N(NC3CC3)C2=C1F DPVCHDCEWZUPRH-ZETCQYMHSA-N 0.000 claims description 2
OPPWHAMEKGQMSO-ZETCQYMHSA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-(cyclopropylamino)-6,8-difluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C1=C(F)C=C2C(=O)N(N)C(=O)N(NC3CC3)C2=C1F OPPWHAMEKGQMSO-ZETCQYMHSA-N 0.000 claims description 2
XSKOMKHOPDOCTI-JTQLQIEISA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-(cyclopropylmethyl)-8-fluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C1=CC=C2C(=O)N(N)C(=O)N(CC3CC3)C2=C1F XSKOMKHOPDOCTI-JTQLQIEISA-N 0.000 claims description 2
YWSUCUHCADKMQR-LURJTMIESA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-5,6,8-trifluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C1=C(F)C(F)=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1F YWSUCUHCADKMQR-LURJTMIESA-N 0.000 claims description 2
RFIZFCOQVQJHIT-QMMMGPOBSA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1[C@@H](N)CCN1C(C(=C1)F)=CC2=C1C(=O)N(N)C(=O)N2C1CC1 RFIZFCOQVQJHIT-QMMMGPOBSA-N 0.000 claims description 2
JPJSIIJEJSBWLK-QMMMGPOBSA-N 3-amino-7-[(3s)-3-aminopyrrolidin-1-yl]-1-ethyl-8-fluoroquinazoline-2,4-dione Chemical compound C=1C=C2C(=O)N(N)C(=O)N(CC)C2=C(F)C=1N1CC[C@H](N)C1 JPJSIIJEJSBWLK-QMMMGPOBSA-N 0.000 claims description 2
ROTWRQJAWBQSOY-PSASIEDQSA-N 3-amino-7-[(3s,4r)-3-amino-4-(trifluoromethyl)pyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1[C@@H](C(F)(F)F)[C@H](N)CN1C1=C(F)C=C2C(=O)N(N)C(=O)N(C3CC3)C2=C1Cl ROTWRQJAWBQSOY-PSASIEDQSA-N 0.000 claims description 2
PQTPQNWFGHUDHR-GOEBONIOSA-N 3-amino-7-[(3s,4r)-3-amino-4-phenylpyrrolidin-1-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound C1([C@@H]2CN(C[C@H]2N)C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)=CC=CC=C1 PQTPQNWFGHUDHR-GOEBONIOSA-N 0.000 claims description 2
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MAXNCKAGFRGUGY-UHFFFAOYSA-N 3-amino-7-[5-(aminomethyl)thiophen-3-yl]-8-chloro-1-cyclopropyl-6-fluoroquinazoline-2,4-dione Chemical compound S1C(CN)=CC(C=2C(=C3C(C(N(N)C(=O)N3C3CC3)=O)=CC=2F)Cl)=C1 MAXNCKAGFRGUGY-UHFFFAOYSA-N 0.000 claims description 2
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CLKAGUACIOUJAC-UHFFFAOYSA-N 3-amino-8-chloro-1-cyclopropyl-7-(2,7-diazaspiro[4.4]nonan-2-yl)-6-fluoroquinazoline-2,4-dione Chemical compound C12=C(Cl)C(N3CC4(CNCC4)CC3)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 CLKAGUACIOUJAC-UHFFFAOYSA-N 0.000 claims description 2
HPYRGTHYPJKOJX-UHFFFAOYSA-N 6-fluoro-1h-quinazolin-2-one Chemical compound C1=C(F)C=CC2=NC(O)=NC=C21 HPYRGTHYPJKOJX-UHFFFAOYSA-N 0.000 claims description 2
YAKDGVOLBBJOLN-UHFFFAOYSA-N 7-(1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridin-6-yl)-3-amino-1-cyclopropyl-6-fluoro-8-methylquinazoline-2,4-dione Chemical compound CC1=C(N2CC3NCCCC3C2)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 YAKDGVOLBBJOLN-UHFFFAOYSA-N 0.000 claims description 2
HTUNFWGEDACBHC-DGCLKSJQSA-N COC1=C2C(=CC(=C1N3C[C@H]([C@@H](C3)C(F)(F)F)CN)F)CN(CN2C4CC4)N Chemical compound COC1=C2C(=CC(=C1N3C[C@H]([C@@H](C3)C(F)(F)F)CN)F)CN(CN2C4CC4)N HTUNFWGEDACBHC-DGCLKSJQSA-N 0.000 claims description 2
HCMNBNDFAABNNL-UHFFFAOYSA-N COCC1(CN)CCNC1 Chemical compound COCC1(CN)CCNC1 HCMNBNDFAABNNL-UHFFFAOYSA-N 0.000 claims description 2
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FGEJNHYAWIIQIE-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)N1CCCC1 FGEJNHYAWIIQIE-UHFFFAOYSA-N 0.000 claims description 2
XMIQMMOCQFIYFM-UHFFFAOYSA-N pyrrolidine-3-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C1CCNC1 XMIQMMOCQFIYFM-UHFFFAOYSA-N 0.000 claims description 2
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LFKDJXLFVYVEFG-UHFFFAOYSA-N tert-butyl carbamate Chemical group CC(C)(C)OC(N)=O LFKDJXLFVYVEFG-UHFFFAOYSA-N 0.000 description 122
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239000000706 filtrate Substances 0.000 description 47
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WJGKQOLBCQGWAL-UHFFFAOYSA-N 3-amino-1-cyclopropyl-6,7-difluoro-8-methoxyquinazoline-2,4-dione Chemical compound COC1=C(F)C(F)=CC(C(N(N)C2=O)=O)=C1N2C1CC1 WJGKQOLBCQGWAL-UHFFFAOYSA-N 0.000 description 44
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238000003818 flash chromatography Methods 0.000 description 37
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239000002253 acid Substances 0.000 description 33
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230000002829 reductive effect Effects 0.000 description 22
238000004440 column chromatography Methods 0.000 description 21
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DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 20
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HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 18
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DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 16
HTURLAGGUMXTAE-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-4,5-difluorobenzoic acid Chemical compound OC(=O)C1=CC(F)=C(F)C=C1NC1=CC=C(F)C=C1F HTURLAGGUMXTAE-UHFFFAOYSA-N 0.000 description 15
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239000003054 catalyst Substances 0.000 description 15
CGIGBVUFCTXFKN-UHFFFAOYSA-N ethyl 2-fluoro-4-pyrrolidin-1-ylbenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC=C1N1CCCC1 CGIGBVUFCTXFKN-UHFFFAOYSA-N 0.000 description 15
229920006395 saturated elastomer Polymers 0.000 description 15
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DPJBLEWIPBSVRY-UHFFFAOYSA-N tert-butyl n-(8-chloro-1-cyclopropyl-6,7-difluoro-2,4-dioxoquinazolin-3-yl)carbamate Chemical compound C12=C(Cl)C(F)=C(F)C=C2C(=O)N(NC(=O)OC(C)(C)C)C(=O)N1C1CC1 DPJBLEWIPBSVRY-UHFFFAOYSA-N 0.000 description 14
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IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
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238000001816 cooling Methods 0.000 description 11
238000000746 purification Methods 0.000 description 11
238000010992 reflux Methods 0.000 description 11
235000017557 sodium bicarbonate Nutrition 0.000 description 11
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JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 10
239000007789 gas Substances 0.000 description 10
239000012038 nucleophile Substances 0.000 description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
238000003756 stirring Methods 0.000 description 10
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150000007660 quinolones Chemical class 0.000 description 9
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 9
JJOOCVNFHZXGPL-UHFFFAOYSA-N tert-butyl n-amino-n-benzoylcarbamate Chemical compound CC(C)(C)OC(=O)N(N)C(=O)C1=CC=CC=C1 JJOOCVNFHZXGPL-UHFFFAOYSA-N 0.000 description 9
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 8
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
239000011521 glass Substances 0.000 description 8
RWZYAGGXGHYGMB-UHFFFAOYSA-N o-aminobenzenecarboxylic acid Natural products NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 8
239000000725 suspension Substances 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 7
VQNBCXNRVVLUKX-UHFFFAOYSA-N 3-amino-7-chloro-1-cyclopropyl-6-fluoropyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C12=NC(Cl)=C(F)C=C2C(=O)N(N)C(=O)N1C1CC1 VQNBCXNRVVLUKX-UHFFFAOYSA-N 0.000 description 7
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 7
229910052794 bromium Inorganic materials 0.000 description 7
244000309464 bull Species 0.000 description 7
238000005658 halogenation reaction Methods 0.000 description 7
239000012948 isocyanate Substances 0.000 description 7
150000002513 isocyanates Chemical class 0.000 description 7
150000002923 oximes Chemical class 0.000 description 7
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
BIJUUEVVGIFXIW-UHFFFAOYSA-N 1-methylquinazoline-2,4-dione hydrochloride Chemical compound Cl.Cn1c2ccccc2c(=O)[nH]c1=O BIJUUEVVGIFXIW-UHFFFAOYSA-N 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 6
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
150000007513 acids Chemical class 0.000 description 6
230000000845 anti-microbial effect Effects 0.000 description 6
239000004599 antimicrobial Substances 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
150000008280 chlorinated hydrocarbons Chemical class 0.000 description 6
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UPMFDOIEEUTSQC-UHFFFAOYSA-N ethyl 3-chloro-2,4,5-trifluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(Cl)=C1F UPMFDOIEEUTSQC-UHFFFAOYSA-N 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
238000005984 hydrogenation reaction Methods 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
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229910052751 metal Inorganic materials 0.000 description 6
239000002184 metal Substances 0.000 description 6
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235000017281 sodium acetate Nutrition 0.000 description 6
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
238000006467 substitution reaction Methods 0.000 description 6
YJUGBLWSKSKQOO-UHFFFAOYSA-N tert-butyl n-amino-n-[3-chloro-2-(cyclopropylamino)-4,5-difluorobenzoyl]carbamate Chemical compound CC(C)(C)OC(=O)N(N)C(=O)C1=CC(F)=C(F)C(Cl)=C1NC1CC1 YJUGBLWSKSKQOO-UHFFFAOYSA-N 0.000 description 6
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 6
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 5
MMBZQEWHXIZIMA-UHFFFAOYSA-N 3-(dibenzylamino)-1-ethyl-6,7-difluoroquinazoline-2,4-dione Chemical compound O=C1N(CC)C2=CC(F)=C(F)C=C2C(=O)N1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 MMBZQEWHXIZIMA-UHFFFAOYSA-N 0.000 description 5
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IHUQJPKASFTOBM-UHFFFAOYSA-N n-(2,4-dinitrophenyl)hydroxylamine Chemical compound ONC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O IHUQJPKASFTOBM-UHFFFAOYSA-N 0.000 description 3
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LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 3
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LHCGUQIZSLMAKQ-UHFFFAOYSA-N 1-(1-benzyl-4-methylpyrrolidin-3-yl)ethanamine Chemical compound C1C(C)C(C(N)C)CN1CC1=CC=CC=C1 LHCGUQIZSLMAKQ-UHFFFAOYSA-N 0.000 description 2
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101150026303 HEX1 gene Proteins 0.000 description 2
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239000002262 Schiff base Substances 0.000 description 2
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230000002378 acidificating effect Effects 0.000 description 2
150000001299 aldehydes Chemical class 0.000 description 2
150000001336 alkenes Chemical class 0.000 description 2
125000003282 alkyl amino group Chemical group 0.000 description 2
150000001356 alkyl thiols Chemical class 0.000 description 2
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
229910021529 ammonia Inorganic materials 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
150000003936 benzamides Chemical class 0.000 description 2
MTZQAGJQAFMTAQ-UHFFFAOYSA-N benzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
WLPUFAZAMBXLPF-UHFFFAOYSA-N benzyl 2,3,4,5,6-pentafluorobenzoate Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1C(=O)OCC1=CC=CC=C1 WLPUFAZAMBXLPF-UHFFFAOYSA-N 0.000 description 2
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VZLUBHTWJFSSEX-UHFFFAOYSA-N benzyl 3-(1-aminoethyl)-3-hydroxypyrrolidine-1-carboxylate Chemical compound C1C(C(N)C)(O)CCN1C(=O)OCC1=CC=CC=C1 VZLUBHTWJFSSEX-UHFFFAOYSA-N 0.000 description 2
PRAYTHAYJVDPMX-UHFFFAOYSA-N benzyl 3-(1-aminoethyl)-3-methoxypyrrolidine-1-carboxylate Chemical compound C1C(OC)(C(C)N)CCN1C(=O)OCC1=CC=CC=C1 PRAYTHAYJVDPMX-UHFFFAOYSA-N 0.000 description 2
XZIJWSOWDHBXHP-UHFFFAOYSA-N benzyl 3-ethylidenepyrrolidine-1-carboxylate Chemical compound C1C(=CC)CCN1C(=O)OCC1=CC=CC=C1 XZIJWSOWDHBXHP-UHFFFAOYSA-N 0.000 description 2
SOVOZYVNLBCFLM-UHFFFAOYSA-N benzyl 3-fluoro-3-(1-methylsulfonyloxyethyl)pyrrolidine-1-carboxylate Chemical compound C1C(C(OS(C)(=O)=O)C)(F)CCN1C(=O)OCC1=CC=CC=C1 SOVOZYVNLBCFLM-UHFFFAOYSA-N 0.000 description 2
FROIAYPDEFQIAE-UHFFFAOYSA-N benzyl 3-fluoro-3-[1-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]pyrrolidine-1-carboxylate Chemical compound C1C(C(NC(=O)OC(C)(C)C)C)(F)CCN1C(=O)OCC1=CC=CC=C1 FROIAYPDEFQIAE-UHFFFAOYSA-N 0.000 description 2
BVHIBSGSGXBXOO-UHFFFAOYSA-N benzyl 3-hydroxy-3-[1-[(2-hydroxyphenyl)methylideneamino]ethyl]pyrrolidine-1-carboxylate Chemical compound C1CN(C(=O)OCC=2C=CC=CC=2)CC1(O)C(C)N=CC1=CC=CC=C1O BVHIBSGSGXBXOO-UHFFFAOYSA-N 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
230000003115 biocidal effect Effects 0.000 description 2
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
229910002091 carbon monoxide Inorganic materials 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
230000003197 catalytic effect Effects 0.000 description 2
238000004296 chiral HPLC Methods 0.000 description 2
229960003405 ciprofloxacin Drugs 0.000 description 2
239000003245 coal Substances 0.000 description 2
OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 2
238000005336 cracking Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
KZZKOVLJUKWSKX-UHFFFAOYSA-N cyclobutanamine Chemical compound NC1CCC1 KZZKOVLJUKWSKX-UHFFFAOYSA-N 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
ZBYMAGSGZVPTJV-UHFFFAOYSA-N ethyl 1-benzyl-3-(methoxymethyl)pyrrolidine-3-carboxylate Chemical compound C1C(C(=O)OCC)(COC)CCN1CC1=CC=CC=C1 ZBYMAGSGZVPTJV-UHFFFAOYSA-N 0.000 description 2
SBHMXBYMQZRRLC-UHFFFAOYSA-N ethyl 2,3,4,5-tetrafluorobenzoate Chemical compound CCOC(=O)C1=CC(F)=C(F)C(F)=C1F SBHMXBYMQZRRLC-UHFFFAOYSA-N 0.000 description 2
GJFOWPZJBADLDJ-UHFFFAOYSA-N ethyl 2,3,4,6-tetrafluorobenzoate Chemical compound CCOC(=O)C1=C(F)C=C(F)C(F)=C1F GJFOWPZJBADLDJ-UHFFFAOYSA-N 0.000 description 2
MLANUBGYWOMWLZ-UHFFFAOYSA-N ethyl 2,3,4-trifluorobenzoate Chemical compound CCOC(=O)C1=CC=C(F)C(F)=C1F MLANUBGYWOMWLZ-UHFFFAOYSA-N 0.000 description 2
VNGUJPHYEQJGMW-UHFFFAOYSA-N ethyl 2,3-difluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(F)C(C(=O)OCC)=CC=C1N1CC(NC(=O)OC(C)(C)C)CC1 VNGUJPHYEQJGMW-UHFFFAOYSA-N 0.000 description 2
USTAENCAYUNVTB-UHFFFAOYSA-N ethyl 2,5-difluoro-3-methyl-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound CC1=C(F)C(C(=O)OCC)=CC(F)=C1N1CC(NC(=O)OC(C)(C)C)CC1 USTAENCAYUNVTB-UHFFFAOYSA-N 0.000 description 2
JAPFJWKJDHOMGJ-UHFFFAOYSA-N ethyl 2,5-difluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC(F)=C1N1CC(NC(=O)OC(C)(C)C)CC1 JAPFJWKJDHOMGJ-UHFFFAOYSA-N 0.000 description 2
RCSVXGMSCAHJGY-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3-ethoxy-5-fluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound CCOC1=C(NC2CC2)C(C(=O)OCC)=CC(F)=C1N1CCC(NC(=O)OC(C)(C)C)C1 RCSVXGMSCAHJGY-UHFFFAOYSA-N 0.000 description 2
XWDXQVZBNAZYEW-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3-fluoro-5-methoxy-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(NC2CC2)C(C(=O)OCC)=CC(OC)=C1N1CCC(NC(=O)OC(C)(C)C)C1 XWDXQVZBNAZYEW-UHFFFAOYSA-N 0.000 description 2
KLDDQZNIRQUHKU-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-5-fluoro-4-pyrrolidin-1-ylbenzoate Chemical compound CCOC(=O)C1=CC(F)=C(N2CCCC2)C=C1NC1CC1 KLDDQZNIRQUHKU-UHFFFAOYSA-N 0.000 description 2
MYSSYHAITZSBEY-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-5-fluoro-6-methylsulfanylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(F)=C(SC)N=C1NC1CC1 MYSSYHAITZSBEY-UHFFFAOYSA-N 0.000 description 2
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FEBASYOFRCJJIS-UHFFFAOYSA-N ethyl 5-chloro-2-(cyclopropylamino)-3-fluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(NC2CC2)C(C(=O)OCC)=CC(Cl)=C1N1CCC(NC(=O)OC(C)(C)C)C1 FEBASYOFRCJJIS-UHFFFAOYSA-N 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
239000012458 free base Substances 0.000 description 2
238000000227 grinding Methods 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
239000005457 ice water Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
JJXINDNYLSMEBI-UHFFFAOYSA-N isocyanato thiohypochlorite Chemical compound ClSN=C=O JJXINDNYLSMEBI-UHFFFAOYSA-N 0.000 description 2
OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 2
FLKMOQAAIRZPTP-UHFFFAOYSA-N methyl 5,6-difluoro-2-methylquinoline-8-carboxylate Chemical compound C1=C(C)N=C2C(C(=O)OC)=CC(F)=C(F)C2=C1 FLKMOQAAIRZPTP-UHFFFAOYSA-N 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 2
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
ZIMCPIQGGYZXRS-UHFFFAOYSA-N n-(cyclopropylcarbamoyl)-3,4,6-trifluoro-2-methylbenzamide Chemical compound CC1=C(F)C(F)=CC(F)=C1C(=O)NC(=O)NC1CC1 ZIMCPIQGGYZXRS-UHFFFAOYSA-N 0.000 description 2
QDLKRVMKDILCHC-UHFFFAOYSA-N n-(cyclopropylcarbamoyl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC(=O)NC1CC1 QDLKRVMKDILCHC-UHFFFAOYSA-N 0.000 description 2
VJPYEYRKXXVWNA-UHFFFAOYSA-N n-(pyrrolidin-3-ylmethyl)propan-2-amine Chemical compound CC(C)NCC1CCNC1 VJPYEYRKXXVWNA-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
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238000011160 research Methods 0.000 description 2
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QZGNLMBAAHIYID-UHFFFAOYSA-N [1-benzyl-3-(methoxymethyl)pyrrolidin-3-yl]methanamine Chemical compound C1C(COC)(CN)CCN1CC1=CC=CC=C1 QZGNLMBAAHIYID-UHFFFAOYSA-N 0.000 description 1
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DZJXKISLUDYJSV-UHFFFAOYSA-N [N].C1CCNC1 Chemical compound [N].C1CCNC1 DZJXKISLUDYJSV-UHFFFAOYSA-N 0.000 description 1
SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
AVRXUQALDJVGAX-UHFFFAOYSA-N [[2-(cyclopropylamino)-3-ethoxy-5-fluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoyl]amino]carbamic acid Chemical compound OC(=O)NNC(=O)C1=CC(F)=C(N2CC(CC2)NC(=O)OC(C)(C)C)C(OCC)=C1NC1CC1 AVRXUQALDJVGAX-UHFFFAOYSA-N 0.000 description 1
IYZBCRMRIRUZTO-UHFFFAOYSA-N [[2-(cyclopropylamino)-3-fluoro-5-methoxy-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoyl]amino]carbamic acid Chemical compound FC1=C(N2CC(CC2)NC(=O)OC(C)(C)C)C(OC)=CC(C(=O)NNC(O)=O)=C1NC1CC1 IYZBCRMRIRUZTO-UHFFFAOYSA-N 0.000 description 1
FZXRBBRJITXWLY-UHFFFAOYSA-N [[2-(cyclopropylamino)-5-fluoro-3-methyl-4-[3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyrrolidin-1-yl]benzoyl]amino]carbamic acid Chemical compound OC(=O)NNC(=O)C1=CC(F)=C(N2CC(CNC(=O)OC(C)(C)C)CC2)C(C)=C1NC1CC1 FZXRBBRJITXWLY-UHFFFAOYSA-N 0.000 description 1
SHUJLLCABBVSJA-UHFFFAOYSA-N [[2-(cyclopropylamino)-5-fluoro-4-[3-methyl-3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]pyrrolidin-1-yl]benzoyl]amino]carbamic acid Chemical compound C1C(CNC(=O)OC(C)(C)C)(C)CCN1C1=CC(NC2CC2)=C(C(=O)NNC(O)=O)C=C1F SHUJLLCABBVSJA-UHFFFAOYSA-N 0.000 description 1
OJTNPLKABFNBMZ-UHFFFAOYSA-N [[3-chloro-2-(cyclopropylamino)-5-fluoro-4-pyrrolidin-1-ylbenzoyl]amino]carbamic acid Chemical compound N1(CCCC1)C1=C(C(=C(C(=O)NNC(=O)O)C=C1F)NC1CC1)Cl OJTNPLKABFNBMZ-UHFFFAOYSA-N 0.000 description 1
QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
FZENGILVLUJGJX-UHFFFAOYSA-N acetaldehyde oxime Chemical compound CC=NO FZENGILVLUJGJX-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
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238000007259 addition reaction Methods 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000004703 alkoxides Chemical class 0.000 description 1
125000005262 alkoxyamine group Chemical group 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
125000004414 alkyl thio group Chemical group 0.000 description 1
AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
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230000009435 amidation Effects 0.000 description 1
238000007112 amidation reaction Methods 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
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VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
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150000001448 anilines Chemical class 0.000 description 1
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239000008346 aqueous phase Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
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150000001540 azides Chemical class 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
UKXSKSHDVLQNKG-UHFFFAOYSA-N benzilic acid Chemical compound C=1C=CC=CC=1C(O)(C(=O)O)C1=CC=CC=C1 UKXSKSHDVLQNKG-UHFFFAOYSA-N 0.000 description 1
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MXSTYZFUEGSFSI-AWEZNQCLSA-N benzyl 2,3,5,6-tetrafluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound C1[C@@H](NC(=O)OC(C)(C)C)CCN1C(C(=C1F)F)=C(F)C(F)=C1C(=O)OCC1=CC=CC=C1 MXSTYZFUEGSFSI-AWEZNQCLSA-N 0.000 description 1
FHCYNCMLCRSWSM-UHFFFAOYSA-N benzyl 2-ethylhexanoate Chemical compound CCCCC(CC)C(=O)OCC1=CC=CC=C1 FHCYNCMLCRSWSM-UHFFFAOYSA-N 0.000 description 1
DPDWHTRNXMSHFE-UHFFFAOYSA-N benzyl 2-ethylpyrrolidine-1-carboxylate Chemical compound CCC1CCCN1C(=O)OCC1=CC=CC=C1 DPDWHTRNXMSHFE-UHFFFAOYSA-N 0.000 description 1
IDXRDMUEZTZLBI-UHFFFAOYSA-N benzyl 3-(1-aminoethyl)-3-fluoropyrrolidine-1-carboxylate Chemical compound C1C(C(N)C)(F)CCN1C(=O)OCC1=CC=CC=C1 IDXRDMUEZTZLBI-UHFFFAOYSA-N 0.000 description 1
HNRGJNVEHLTNBK-UHFFFAOYSA-N benzyl 3-fluoro-3-(1-hydroxyethyl)pyrrolidine-1-carboxylate Chemical compound C1C(C(O)C)(F)CCN1C(=O)OCC1=CC=CC=C1 HNRGJNVEHLTNBK-UHFFFAOYSA-N 0.000 description 1
DGQYMNWQXVFIBE-UHFFFAOYSA-N benzyl 3-fluoropyrrolidine-1-carboxylate Chemical compound C1C(F)CCN1C(=O)OCC1=CC=CC=C1 DGQYMNWQXVFIBE-UHFFFAOYSA-N 0.000 description 1
OANNHHUDLXAWBH-UHFFFAOYSA-N benzyl 3-methoxy-3-[1-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]pyrrolidine-1-carboxylate Chemical compound C1C(OC)(C(C)NC(=O)OC(C)(C)C)CCN1C(=O)OCC1=CC=CC=C1 OANNHHUDLXAWBH-UHFFFAOYSA-N 0.000 description 1
LMHWEUQNJRXMCD-UHFFFAOYSA-N benzyl 3-oxopyrrolidine-1-carboxylate Chemical compound C1CC(=O)CN1C(=O)OCC1=CC=CC=C1 LMHWEUQNJRXMCD-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
125000001743 benzylic group Chemical group 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
238000007664 blowing Methods 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
150000001642 boronic acid derivatives Chemical class 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
RUEKPBLTWGFBOD-UHFFFAOYSA-N bromoethyne Chemical group BrC#C RUEKPBLTWGFBOD-UHFFFAOYSA-N 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
239000010974 bronze Substances 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
229910000024 caesium carbonate Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
239000000292 calcium oxide Substances 0.000 description 1
ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
OWIUPIRUAQMTTK-UHFFFAOYSA-N carbazic acid Chemical compound NNC(O)=O OWIUPIRUAQMTTK-UHFFFAOYSA-N 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
125000002843 carboxylic acid group Chemical group 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000004517 catalytic hydrocracking Methods 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
239000002738 chelating agent Substances 0.000 description 1
238000007385 chemical modification Methods 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
KVSASDOGYIBWTA-UHFFFAOYSA-N chloro benzoate Chemical compound ClOC(=O)C1=CC=CC=C1 KVSASDOGYIBWTA-UHFFFAOYSA-N 0.000 description 1
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940125758 compound 15 Drugs 0.000 description 1
229940126142 compound 16 Drugs 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
229940126086 compound 21 Drugs 0.000 description 1
229940126208 compound 22 Drugs 0.000 description 1
229940125833 compound 23 Drugs 0.000 description 1
229940125961 compound 24 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
229940125851 compound 27 Drugs 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
229940125877 compound 31 Drugs 0.000 description 1
229940125878 compound 36 Drugs 0.000 description 1
229940125807 compound 37 Drugs 0.000 description 1
229940127573 compound 38 Drugs 0.000 description 1
229940126540 compound 41 Drugs 0.000 description 1
229940125936 compound 42 Drugs 0.000 description 1
229940125844 compound 46 Drugs 0.000 description 1
229940127271 compound 49 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
229940126545 compound 53 Drugs 0.000 description 1
229940125900 compound 59 Drugs 0.000 description 1
229940126179 compound 72 Drugs 0.000 description 1
150000001879 copper Chemical class 0.000 description 1
KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 1
NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
229940076286 cupric acetate Drugs 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
238000005695 dehalogenation reaction Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
125000006371 dihalo methyl group Chemical group 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
GZJCUHWAHMQQNH-UHFFFAOYSA-L disodium sulfite decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])=O GZJCUHWAHMQQNH-UHFFFAOYSA-L 0.000 description 1
239000002934 diuretic Substances 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000012039 electrophile Substances 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
238000010931 ester hydrolysis Methods 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
QPMJENKZJUFOON-PLNGDYQASA-N ethyl (z)-3-chloro-2-cyano-4,4,4-trifluorobut-2-enoate Chemical compound CCOC(=O)C(\C#N)=C(/Cl)C(F)(F)F QPMJENKZJUFOON-PLNGDYQASA-N 0.000 description 1
PLHHLRVGWNGWPX-JTQLQIEISA-N ethyl 2,3,5-trifluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(F)C(C(=O)OCC)=CC(F)=C1N1C[C@@H](NC(=O)OC(C)(C)C)CC1 PLHHLRVGWNGWPX-JTQLQIEISA-N 0.000 description 1
BWNOFHKEKFPTBV-JTQLQIEISA-N ethyl 2,3,6-trifluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(F)C(C(=O)OCC)=C(F)C=C1N1C[C@@H](NC(=O)OC(C)(C)C)CC1 BWNOFHKEKFPTBV-JTQLQIEISA-N 0.000 description 1
DWRVQRRMMIQTBY-UHFFFAOYSA-N ethyl 2,3-difluoro-5-methoxy-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(F)C(C(=O)OCC)=CC(OC)=C1N1CC(NC(=O)OC(C)(C)C)CC1 DWRVQRRMMIQTBY-UHFFFAOYSA-N 0.000 description 1
AQTKJIVKYZAFNJ-UHFFFAOYSA-N ethyl 2,5-difluoro-3-methoxy-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound COC1=C(F)C(C(=O)OCC)=CC(F)=C1N1CC(NC(=O)OC(C)(C)C)CC1 AQTKJIVKYZAFNJ-UHFFFAOYSA-N 0.000 description 1
LRIZYRFXKQSOFG-UHFFFAOYSA-N ethyl 2,5-difluoro-4-pyrrolidin-1-ylbenzoate Chemical compound C1=C(F)C(C(=O)OCC)=CC(F)=C1N1CCCC1 LRIZYRFXKQSOFG-UHFFFAOYSA-N 0.000 description 1
NSABSAJYHZYYMK-ZDUSSCGKSA-N ethyl 2-(cyclopropylamino)-3,6-difluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(NC2CC2)C(C(=O)OCC)=C(F)C=C1N1CC[C@H](NC(=O)OC(C)(C)C)C1 NSABSAJYHZYYMK-ZDUSSCGKSA-N 0.000 description 1
RCKVZZTXQFAAPT-UHFFFAOYSA-N ethyl 2-(cyclopropylamino)-3-fluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(NC2CC2)C(C(=O)OCC)=CC=C1N1CCC(NC(=O)OC(C)(C)C)C1 RCKVZZTXQFAAPT-UHFFFAOYSA-N 0.000 description 1
KOWLMUHLYWGECF-UHFFFAOYSA-N ethyl 2-chloro-5-fluoro-6-methylsulfanylpyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(F)=C(SC)N=C1Cl KOWLMUHLYWGECF-UHFFFAOYSA-N 0.000 description 1
CINXGNHRKLMYRK-UHFFFAOYSA-N ethyl 2-cyclopropylideneacetate Chemical compound CCOC(=O)C=C1CC1 CINXGNHRKLMYRK-UHFFFAOYSA-N 0.000 description 1
GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
XITYZNUXHDHZKA-JTQLQIEISA-N ethyl 3-chloro-2,5-difluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound ClC1=C(F)C(C(=O)OCC)=CC(F)=C1N1C[C@@H](NC(=O)OC(C)(C)C)CC1 XITYZNUXHDHZKA-JTQLQIEISA-N 0.000 description 1
XITYZNUXHDHZKA-UHFFFAOYSA-N ethyl 3-chloro-2,5-difluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound ClC1=C(F)C(C(=O)OCC)=CC(F)=C1N1CC(NC(=O)OC(C)(C)C)CC1 XITYZNUXHDHZKA-UHFFFAOYSA-N 0.000 description 1
KDKBIFLYOSNINK-ZDUSSCGKSA-N ethyl 3-chloro-2-(cyclopropylamino)-5-fluoro-4-[(3s)-3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound ClC1=C(NC2CC2)C(C(=O)OCC)=CC(F)=C1N1CC[C@H](NC(=O)OC(C)(C)C)C1 KDKBIFLYOSNINK-ZDUSSCGKSA-N 0.000 description 1
FCWLRKKKNGDVQE-UHFFFAOYSA-N ethyl 5-benzyl-5-azaspiro[2.4]heptane-2-carboxylate Chemical compound CCOC(=O)C1CC11CN(CC=2C=CC=CC=2)CC1 FCWLRKKKNGDVQE-UHFFFAOYSA-N 0.000 description 1
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ILCZUEOFLWBQFZ-UHFFFAOYSA-N ethyl 5-chloro-2,3-difluoro-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]pyrrolidin-1-yl]benzoate Chemical compound FC1=C(F)C(C(=O)OCC)=CC(Cl)=C1N1CC(NC(=O)OC(C)(C)C)CC1 ILCZUEOFLWBQFZ-UHFFFAOYSA-N 0.000 description 1
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238000001727 in vivo Methods 0.000 description 1
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229910052742 iron Inorganic materials 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
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150000003456 sulfonamides Chemical class 0.000 description 1
150000003457 sulfones Chemical group 0.000 description 1
GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
206010042772 syncope Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 1
WZXAUWOKROJGPO-BAUSSPIASA-N tert-butyl carbamate;(3s,4r)-4-phenylpyrrolidin-3-amine Chemical compound CC(C)(C)OC(N)=O.N[C@@H]1CNC[C@H]1C1=CC=CC=C1 WZXAUWOKROJGPO-BAUSSPIASA-N 0.000 description 1
IXZDIALLLMRYOU-UHFFFAOYSA-N tert-butyl hypochlorite Chemical compound CC(C)(C)OCl IXZDIALLLMRYOU-UHFFFAOYSA-N 0.000 description 1
HOLFKYFPAJFTQK-UHFFFAOYSA-N tert-butyl n-(1-piperidin-3-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1CCCNC1 HOLFKYFPAJFTQK-UHFFFAOYSA-N 0.000 description 1
HJUZGKGDCUOVML-UHFFFAOYSA-N tert-butyl n-(1-pyrrolidin-3-ylethyl)carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1CCNC1 HJUZGKGDCUOVML-UHFFFAOYSA-N 0.000 description 1
UIYMGRQQGQOESZ-UHFFFAOYSA-N tert-butyl n-(3-azabicyclo[3.1.0]hexan-1-ylmethyl)carbamate Chemical compound C1NCC2(CNC(=O)OC(C)(C)C)C1C2 UIYMGRQQGQOESZ-UHFFFAOYSA-N 0.000 description 1
XUJWYCDSISOQPK-UHFFFAOYSA-N tert-butyl n-(3-methylpyrrolidin-1-yl)carbamate Chemical compound CC1CCN(NC(=O)OC(C)(C)C)C1 XUJWYCDSISOQPK-UHFFFAOYSA-N 0.000 description 1
HOVWKJWUCRVIBO-UHFFFAOYSA-N tert-butyl n-(5-azaspiro[2.4]heptan-7-ylmethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCC1CNCC11CC1 HOVWKJWUCRVIBO-UHFFFAOYSA-N 0.000 description 1
HJUZGKGDCUOVML-BDAKNGLRSA-N tert-butyl n-[(1r)-1-[(3s)-pyrrolidin-3-yl]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C)[C@H]1CCNC1 HJUZGKGDCUOVML-BDAKNGLRSA-N 0.000 description 1
AXCFIJFQUMHJRG-UHFFFAOYSA-N tert-butyl n-[(3-methylpyrrolidin-3-yl)methyl]carbamate Chemical compound CC(C)(C)OC(=O)NCC1(C)CCNC1 AXCFIJFQUMHJRG-UHFFFAOYSA-N 0.000 description 1
ONUYBIHANMIKNX-UHFFFAOYSA-N tert-butyl n-[(3-phenylpyrrolidin-3-yl)methyl]carbamate Chemical compound C=1C=CC=CC=1C1(CNC(=O)OC(C)(C)C)CCNC1 ONUYBIHANMIKNX-UHFFFAOYSA-N 0.000 description 1
LSVBXCZRQALHKY-ZDUSSCGKSA-N tert-butyl n-[(3s)-1-[3-(cyclopropylamino)-2,5,6-trifluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]carbamoyl]phenyl]pyrrolidin-3-yl]carbamate Chemical compound FC1=C(NC2CC2)C(C(=O)NNC(=O)OC(C)(C)C)=C(F)C(F)=C1N1CC[C@H](NC(=O)OC(C)(C)C)C1 LSVBXCZRQALHKY-ZDUSSCGKSA-N 0.000 description 1
TTZLWOFPFKRYBC-RNFRBKRXSA-N tert-butyl n-[(3s,4r)-4-(trifluoromethyl)pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CNC[C@H]1C(F)(F)F TTZLWOFPFKRYBC-RNFRBKRXSA-N 0.000 description 1
BKITXDSDJGOXPN-HTQZYQBOSA-N tert-butyl n-[(3s,4r)-4-methylpyrrolidin-3-yl]carbamate Chemical compound C[C@@H]1CNC[C@H]1NC(=O)OC(C)(C)C BKITXDSDJGOXPN-HTQZYQBOSA-N 0.000 description 1
UAWBFPVQUJUVQG-UHFFFAOYSA-N tert-butyl n-[1-(4-methylpyrrolidin-3-yl)ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(C)C1CNCC1C UAWBFPVQUJUVQG-UHFFFAOYSA-N 0.000 description 1
UKXZEKOMLQUGDZ-UHFFFAOYSA-N tert-butyl n-[1-[2-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]carbamoyl]-5-(propan-2-ylamino)phenyl]pyrrolidin-3-yl]carbamate Chemical compound C1=C(C(=O)NNC(=O)OC(C)(C)C)C(NC(C)C)=CC(N2CC(CC2)NC(=O)OC(C)(C)C)=C1F UKXZEKOMLQUGDZ-UHFFFAOYSA-N 0.000 description 1
DBZPVFMDQGPXNE-UHFFFAOYSA-N tert-butyl n-[1-[3-(cyclopropylamino)-2-ethoxy-6-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]carbamoyl]phenyl]pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)C1=CC(F)=C(N2CC(CC2)NC(=O)OC(C)(C)C)C(OCC)=C1NC1CC1 DBZPVFMDQGPXNE-UHFFFAOYSA-N 0.000 description 1
JNDXEWAHNFZPOB-UHFFFAOYSA-N tert-butyl n-[1-[3-(cyclopropylamino)-2-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]carbamoyl]phenyl]pyrrolidin-3-yl]carbamate Chemical compound FC1=C(NC2CC2)C(C(=O)NNC(=O)OC(C)(C)C)=CC=C1N1CCC(NC(=O)OC(C)(C)C)C1 JNDXEWAHNFZPOB-UHFFFAOYSA-N 0.000 description 1
AFMAMAZBTWCOOI-UHFFFAOYSA-N tert-butyl n-[1-[5-(cyclobutylamino)-2-fluoro-4-[[(2-methylpropan-2-yl)oxycarbonylamino]carbamoyl]phenyl]pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)NNC(=O)C1=CC(F)=C(N2CC(CC2)NC(=O)OC(C)(C)C)C=C1NC1CCC1 AFMAMAZBTWCOOI-UHFFFAOYSA-N 0.000 description 1
GWYXCNXINAWWBV-JGVFFNPUSA-N tert-butyl n-[[(3s,4s)-4-(trifluoromethyl)pyrrolidin-3-yl]methyl]carbamate Chemical compound CC(C)(C)OC(=O)NC[C@@H]1CNC[C@H]1C(F)(F)F GWYXCNXINAWWBV-JGVFFNPUSA-N 0.000 description 1
LJFKNKLHLHGEGF-UHFFFAOYSA-N tert-butyl n-amino-n-[2-(cyclopropylamino)-5-fluoro-4-[3-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]piperidin-1-yl]benzoyl]carbamate Chemical compound C1C(CNC(=O)OC(C)(C)C)CCCN1C1=CC(NC2CC2)=C(C(=O)N(N)C(=O)OC(C)(C)C)C=C1F LJFKNKLHLHGEGF-UHFFFAOYSA-N 0.000 description 1
BSJLOBHRTVICMV-UHFFFAOYSA-N tert-butyl n-amino-n-[5-chloro-2-(cyclopropylamino)-4-fluorobenzoyl]carbamate Chemical compound CC(C)(C)OC(=O)N(N)C(=O)C1=CC(Cl)=C(F)C=C1NC1CC1 BSJLOBHRTVICMV-UHFFFAOYSA-N 0.000 description 1
IZIQFESBSDHONG-UHFFFAOYSA-N tert-butyl n-benzoyl-n-(chloroamino)carbamate Chemical compound CC(C)(C)OC(=O)N(NCl)C(=O)C1=CC=CC=C1 IZIQFESBSDHONG-UHFFFAOYSA-N 0.000 description 1
RARMMJLRNFXCRR-UHFFFAOYSA-N tert-butyl n-ethyl-n-(4-fluoropyrrolidin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)N(CC)C1CNCC1F RARMMJLRNFXCRR-UHFFFAOYSA-N 0.000 description 1
ISTGQSQWSKCNFJ-UHFFFAOYSA-N tert-butyl n-ethylcarbamate Chemical compound CCNC(=O)OC(C)(C)C ISTGQSQWSKCNFJ-UHFFFAOYSA-N 0.000 description 1
INNYIYVRIWAQJS-UHFFFAOYSA-N tert-butyl n-hexyl-n-methylcarbamate Chemical compound CCCCCCN(C)C(=O)OC(C)(C)C INNYIYVRIWAQJS-UHFFFAOYSA-N 0.000 description 1
JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 1
IUHRDCVRNBKBMO-UHFFFAOYSA-N tert-butyl n-pyrrolidin-1-ylcarbamate Chemical compound CC(C)(C)OC(=O)NN1CCCC1 IUHRDCVRNBKBMO-UHFFFAOYSA-N 0.000 description 1
239000012414 tert-butyl nitrite Substances 0.000 description 1
ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
JYEVUDXCQHLXNG-UHFFFAOYSA-N tert-butyl pyridine-3-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CC=CN=C1 JYEVUDXCQHLXNG-UHFFFAOYSA-N 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
150000003557 thiazoles Chemical class 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
125000005309 thioalkoxy group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
238000012546 transfer Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
125000004665 trialkylsilyl group Chemical group 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000004953 trihalomethyl group Chemical group 0.000 description 1
PQDJYEQOELDLCP-UHFFFAOYSA-N trimethylsilane Chemical compound C[SiH](C)C PQDJYEQOELDLCP-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
AQLJVWUFPCUVLO-UHFFFAOYSA-N urea hydrogen peroxide Chemical compound OO.NC(N)=O AQLJVWUFPCUVLO-UHFFFAOYSA-N 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/10—Spiro-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Animal Behavior & Ethology (AREA)
Communicable Diseases (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Virology (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Molecular Biology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Paper (AREA)

KR1020027009515A 2000-01-24 2000-12-12 3-아미노퀴나졸린-2,4-디온 항균제 Withdrawn KR20020067701A (ko)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US17825200P	2000-01-24	2000-01-24
US60/178,252		2000-01-24
US24126700P	2000-10-18	2000-10-18
US60/241,267		2000-10-18
PCT/US2000/033656 WO2001053273A1 (en)	2000-01-24	2000-12-12	3-aminoquinazolin-2,4-dione antibacterial agents

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Publication Number	Publication Date
KR20020067701A true KR20020067701A (ko)	2002-08-23

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Country Status (38)

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US (2)	US7094780B1 (es)
EP (1)	EP1255739B1 (es)
JP (1)	JP4811978B2 (es)
KR (1)	KR20020067701A (es)
CN (1)	CN1425008A (es)
AP (1)	AP2002002603A0 (es)
AR (1)	AR030186A1 (es)
AT (1)	ATE398110T1 (es)
AU (1)	AU783078B2 (es)
BG (1)	BG107023A (es)
BR (1)	BR0017010A (es)
CA (1)	CA2393802C (es)
CO (1)	CO5320600A1 (es)
CR (1)	CR6709A (es)
DE (1)	DE60039194D1 (es)
EA (1)	EA005585B1 (es)
EE (1)	EE200200412A (es)
ES (1)	ES2304992T3 (es)
GE (1)	GEP20053429B (es)
HK (1)	HK1054237A1 (es)
HN (1)	HN2001000009A (es)
HR (1)	HRP20020696A2 (es)
HU (1)	HUP0204101A3 (es)
IL (1)	IL150393A0 (es)
IS (1)	IS6448A (es)
MA (1)	MA26866A1 (es)
MX (1)	MXPA02005989A (es)
NO (1)	NO20023516D0 (es)
OA (1)	OA12316A (es)
PA (1)	PA8510101A1 (es)
PE (1)	PE20011060A1 (es)
PL (1)	PL356837A1 (es)
SK (1)	SK10572002A3 (es)
SV (1)	SV2001000288A (es)
TN (1)	TNSN01011A1 (es)
UY (1)	UY26551A1 (es)
WO (1)	WO2001053273A1 (es)
YU (1)	YU55902A (es)

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EP1667994A1 (en) *	2003-09-12	2006-06-14	Warner-Lambert Company LLC	Quinolone antibacterial agents
WO2005026153A1 (en) *	2003-09-12	2005-03-24	Warner-Lambert Company Llc	Quinazoline-2, 4-diones as antibacterial agents
BRPI0416708A (pt) *	2003-11-18	2007-01-16	Warner Lambert Co	derivados de aminoquinazolidinadiona antibacterianos
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GB0416730D0 (en)	2004-07-27	2004-09-01	Novartis Ag	Organic compounds
ATE447572T1 (de) *	2005-01-26	2009-11-15	Hoffmann La Roche	Phenylmethanonderivate und ihre verwendung als glycin-transporter-1-hemmer
GB0507298D0 (en) *	2005-04-11	2005-05-18	Novartis Ag	Organic compounds
US7977346B2 (en)	2006-01-17	2011-07-12	Guoqing Paul Chen	Spiro compounds and methods of use
KR101084521B1 (ko)	2006-03-28	2011-11-18	워너 칠콧 컴퍼니 엘엘씨	퀴놀론 중간체를 제조하기 위한 커플링 방법
DK2001862T3 (da)	2006-03-28	2011-08-08	Warner Chilcott Co Llc	Malatsalte og polymorfe af (3S,5S)-7-[3-amino-5-methyl-piperidinyl]-1-cyklopropyl-1,4-dihydro-8-methoxy-4-oxo-3-quinolincarboxylsyre
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PT2239257E (pt) *	2008-01-30	2012-09-12	Shin Poong Pharmaceutical Co Ltd	Novo derivado de quinazolina-2,4-diona e composições médicas para a profilaxia e tratamento da doença dos nervos cranianos contendo o dito derivado
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MX345780B (es)	2011-03-15	2017-02-15	Trius Therapeutics Inc	Inhibidores triciclicos de girasa.
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Publication number	Publication date
PL356837A1 (en)	2004-07-12
EP1255739A1 (en)	2002-11-13
TNSN01011A1 (en)	2005-11-10
ATE398110T1 (de)	2008-07-15
ES2304992T3 (es)	2008-11-01
US7582627B2 (en)	2009-09-01
CR6709A (es)	2003-11-25
CA2393802C (en)	2011-04-19
DE60039194D1 (de)	2008-07-24
JP2003520277A (ja)	2003-07-02
WO2001053273A1 (en)	2001-07-26
AU2089901A (en)	2001-07-31
PA8510101A1 (es)	2003-06-30
NO20023516L (no)	2002-07-23
US20060183762A1 (en)	2006-08-17
YU55902A (sh)	2006-01-16
IS6448A (is)	2002-06-27
BG107023A (en)	2003-04-30
MA26866A1 (fr)	2004-12-20
MXPA02005989A (es)	2002-10-23
UY26551A1 (es)	2001-04-30
US7094780B1 (en)	2006-08-22
HK1054237A1 (zh)	2003-11-21
EA200200661A1 (ru)	2003-02-27
EP1255739B1 (en)	2008-06-11
HUP0204101A2 (hu)	2003-04-28
JP4811978B2 (ja)	2011-11-09
IL150393A0 (en)	2002-12-01
PE20011060A1 (es)	2001-10-12
SV2001000288A (es)	2001-11-30
OA12316A (en)	2006-05-15
US20060287308A1 (en)	2006-12-21
AP2002002603A0 (en)	2002-09-30
HUP0204101A3 (en)	2004-05-28
BR0017010A (pt)	2002-11-05
CO5320600A1 (es)	2003-09-30
EE200200412A (et)	2003-10-15
HN2001000009A (es)	2001-06-13
EA005585B1 (ru)	2005-04-28
GEP20053429B (en)	2005-01-25
AU783078B2 (en)	2005-09-22
CA2393802A1 (en)	2001-07-26
CN1425008A (zh)	2003-06-18
SK10572002A3 (sk)	2003-10-07
NO20023516D0 (no)	2002-07-23
AR030186A1 (es)	2003-08-13
HRP20020696A2 (en)	2003-12-31

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